This Center for Cancer Nanotechnology Excellence and Translation (CCNE-T) brings together scientists and physicians from Stanford University, University of California Berkeley/Lawrence Berkeley National Lab, University of California Los Angeles, University of Southern California and the Massachusetts Institute of Technology. The grant also leverages on several activities in cancer biomarker discovery/validation with the Canary Foundation and the Fred Hutchinson Cancer Center. This research proposal is centered around our vision that in vitro diagnostics used in conjunction with in vivo diagnostics can markedly impact future cancer patient management. Furthermore, we believe that nanotechnology can significantly advance both in vitro diagnostics through proteomic nanosensors and in vivo diagnostics through nanoparticles for molecular imaging. The cancer-related biochemical pathways targeted will be the Herkinase axis with a focus on predicting and monitoring response to lung cancer therapy. An additional focus will be on the earlier detection of Ovarian Cancer We have assembled a highly interdisciplinary team of scientists from the fields of chemistry, materials science and engineering, molecular imaging, oncology, cancer biology, protein engineering, and mathematical modeling in order to accomplish our goals. We highly leverage resources at the Stanford Bio-X and Nanoscale Science and Engineering Programs, the California Nanosystems Institute, and the Cancer Centers of Stanford/UCL/VUSC/Fred Hutchinson. We will utilize significant resources at several small companies we have started and General Electric. We have direct links to a Fred Hutchinson Ovarian SPORE, a recently funded Physical Sciences Oncology Center (PSOC), the ICMIC P50, ICBP, and NTR at Stanford. Furthermore, the Canary Foundation will provide more than $3M towards clinical trials to translate our nanotechnologies and help with outreach. Four research projects and three cores are proposed. Project #1 focuses on novel smart nanoparticles including Raman and self-assembling nanoparticles, Project #2 focuses on the use of magneto-nanotechnology for blood proteomics and cell sorting. Project #3 focuses on the use of multiple nano-platforms to interrogate single circulating tumor cells. Project #4 focuses on molecular imaging of ovarian cancer with photoacoustics and Raman nanoparticles, and monitoring response to therapy using imaging and magneto-nanosensors. Core #1 will facilitate Nanoinformatics, Core #2 will provide resources for nanocharacterization and nanofabrication, Core #3 will facilitate clinical translation by linking our nanotechnologies to existing patient samples and ongoing as well as new clinical trials. With our highly interactive and cohesive program focused on developing and validating nanotechnology for anti-cancer therapy response and earlier cancer detection, we will imagine, invent, and innovate for the benefit of cancer patients.